Lyme disease is a tick-transmitted infection caused by a newly recognized Borrelia burgdorferi. The illness, which affects both children and adults, usually begins with a characteristic skin lesion, erythema migrans, which may be followed by meningitis, cranial or peripheral neuritis, myocarditis, or arthritis. Our work covers the natural history, diagnosis, treatment, epidemiology, and pathogenesis of this disorder. During the next granting period, studies of the natural history of the illness will be continued in patients with arthritis, CNS abnormalities, acrodermatitis chronica atrophicans, or maternal-fetal illness. Sensitive and specific diagnostic tests will be developed for early disease and for neurologic abnormalities, and clinically useful evidence for persistent immunologic and inflammatory stimulation will be sought through serial measurements in plasma of Interleukin-1 (and its endogenous inhibitors), C-reactive protein, and fibrinopeptide A. Antibiotic therapy regimens will be tested in patients with arthritis, and the role of arthroscopic synovectomy will be assessed in unresponsive cases. The frequency, duration, and risk of asymptomatic infection will be ascertained in defined populations. To further understand the pathogenesis of the arthritis, monoclonal antibodies will be generated against B. burgdorferi and against the idiotypes of anti-B. burgdorferi, which will be used to search for B. burdorferi in synovium, to look for evidence of molecular mimicry or peptidoglycan, and to explore the specificities of the immune response in this tissue. Spirochetal antigens will be sought within immune complexes in serum and joint fluid. An animal model for Lyme disease will be sought to further understand pathogenetic mechanisms. With collaborators, the frequency and role of certain autoantibodies will be defined, immunogenetic profiles will be determined using typing sera and alloreactive T cell clones, and lymphocyte-endothelial cell interactions will be investigated in synovium. This work will provide important information about the diagnosis and treatment of Lyme disease, and may have implications for other rheumatic diseases.